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The beneficial effect of anti-TNF-α therapy in AS might not only neutralize the effects of TNF-α but also down-regulate Th17 and Th17-related cytokines accompanied by up-regulating the Treg/TGF-β axis in responders.

Diabetes is one of common endocrine and metabolic disorder diseases, and it leads to multiple complications causing uncountable suffering and incalculable economic losses to worldwide patients. 1 Globally, the number of people with diabetes mellitus has quadrupled in the past three decades. About 1 in 11 adults now have diabetes mellitus, and 90% of them are type 2 diabetes. 2 Diabetes has increasingly become a global problem to be solved urgently.

Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature that involves the loss of endothelial function together with inappropriate smooth muscle cell growth, inflammation, and fibrosis. These changes underlie a progressive remodeling of blood vessels that alters flow and increases pulmonary blood pressure. Elevated pressures in the pulmonary artery imparts a chronic stress on the right ventricle which undergoes compensatory hypertrophy but eventually fails. How PAH develops remains incompletely understood and evidence for the altered production of reactive oxygen and nitrogen species (ROS, RNS respectively) in the pulmonary circulation has been well documented. There are many different types of ROS and RNS, multiple sources, and collective actions and interactions. This review summarizes past and current knowledge of the sources of ROS and RNS and how they may contribute to the loss of endothelial function and changes in smooth muscle proliferation in the pulmonary circulation.

A defining characteristic of pulmonary hypertension (PH) is the extensive remodeling of pulmonary arteries (PAs), which results in progressive increases in vascular resistance and stiffness and eventual failure of the right ventricle. There is no cure for PH and identification of novel molecular mechanisms that underlie increased proliferation, reduced apoptosis, and excessive extracellular matrix production in pulmonary artery smooth muscle cells (PASMCs) is a vital objective. Galectin-3 (Gal-3) is a chimeric lectin and potent driver of many aspects of fibrosis, but its role in regulating PASMC behavior in PH remains poorly understood. Herein, we evaluated the importance of increased Gal-3 expression and signaling on PA vascular remodeling and cardiopulmonary function in experimental models of PH. Gal-3 expression was quantified by qRT-PCR, immunoblotting, and immunofluorescence imaging, and its functional role was assessed by specific Gal-3 inhibitors and CRISPR/Cas9-mediated knockout of Gal-3 in the rat. In rat models of PH, we observed increased Gal-3 expression in PASMCs, which stimulated migration and resistance to apoptosis, whereas silencing or genetic deletion reduced cellular migration and PA fibrosis and increased apoptosis. Gal-3 inhibitors attenuated and reversed PA remodeling and fibrosis, as well as hemodynamic indices in monocrotaline (MCT)-treated rats in vivo. These results were supported by genetic deletion of Gal-3 in both MCT and Sugen Hypoxia rat models. In conclusion, our results suggest that elevated Gal-3 levels contribute to inappropriate PA remodeling in PH by enhancing multiple profibrotic mechanisms. Therapeutic strategies targeting Gal-3 may be of benefit in the treatment of PH.

Enthesitis is considered as the primary anatomical lesion in ankylosing spondylitis (AS). We aimed to investigate the potential of ultrasound to detect early changes after TNF-a antagonist therapy of Achilles enthesitis of AS patients. One hundred AS patients with active disease, requiring TNF-a antagonist therapy, were included (etanercept n = 25, infliximab n = 25, adalimumab n = 25, non-biologic disease-modifying antirheumatic drugs (DMARDs) n = 25). Physical examination was performed to evaluate disease activity and detect Achilles enthesitis and/or retrocalcaneal bursitis. Ultrasound of the Achilles enthesitis was performed bilaterally. Follow-up examinations were performed 3 months after the initiation of therapy. Gray scale (GS) scores, Power Doppler (PD) scores, and total additive scores (TS) decreased significantly during TNF-a antagonist therapy but not in traditional non-biologic traditional DMARDs group. The bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis metrology index (BASMI), bath ankylosing spondylitis functional index (BASFI), and Maastricht ankylosing spondylitis enthesitis score (MASES) all showed significant improvements. When three different TNF-a antagonists were analyzed separately, no significant difference was observed in GS, PD, and total scores. Subclinical Achilles enthesitis, detected only with GS ultrasound, is present in a subset of AS patients and a significant improvement can be demonstrated after 3 months of TNF-a antagonist therapy. Doppler ultrasound provides a reliable estimation to monitor the therapeutic response to TNF antagonists in AS patients with Achilles enthesitis. TNF-a antagonists have been shown to be effective in decreasing ultrasound signs of enthesitis after 3 months of therapy in AS patients.

IntroductionActivated platelets exert a proinflammatory action that can be largely ascribed to their ability to interact with monocytes. However, the mechanisms that promote dynamic changes in monocyte subsets in rheumatoid arthritis (RA) have not been clearly identified. The aim of this study was to determine whether platelet activation and the consequent formation of monocyte-platelet aggregates (MPA) might induce a proinflammatory phenotype in circulating monocytes in RA.MethodsThe surface phenotype of platelets and the frequencies of monocyte subpopulations in the peripheral blood of RA patients were determined using flow cytometry. Platelets were sorted and co-cultured with monocytes. In addition, monocyte activation was assessed by measuring the nuclear factor kappa B (NF-κB) pathway. The disease activity was evaluated using the 28-joint disease activity score.ResultsPlatelet activation, circulating intermediate monocytes (Mon2) and MPA formation were significantly elevated in RA, especially in those with active disease status. Furthermore, Mon2 monocytes showed higher CD147 expression and responded to direct cell contact with activated platelets with higher cytokine production and matrix metallopeptidase 9 (MMP-9) secretion, which increased the expression of CD147. After the addition of specific antibodies for CD147, those effects were abolished. Furthermore, the NF-κB-driven inflammatory pathway may be involved in this process.ConclusionsThese findings indicate an important role of platelet activation and the consequent formation of MPA in the generation of the proinflammatory cytokine milieu and for the promotion and maintenance of the pathogenically relevant Mon2 monocyte compartment in RA, which is likely to play an important role in the pathogenesis of autoimmunity.

0.727-0.840), but mortality in women who used CPAP increased (odds ratio, 1.320; 95% confidence interval, 1.151-1.515). In men, significant interactions were found for cerebrovascular disease, diabetes mellitus, and hypertension, but patients treated with CPAP had a lower probability of death than control subjects in all scenarios (Table 1). On the other hand, CPAP treatment was associated with lower mortality in women with cerebrovascular disease but had a neutral or detrimental effect on mortality in other scenarios (Table 1). Overall, the population of patients treated with CPAP in Catalonia had lower mortality rates than age-, sex-, and regionmatched control subjects, despite a higher prevalence of most comorbidities among patients treated with CPAP. However, this finding was driven by the 74% of men in the population, because CPAP was associated with increased mortality among women. These population-based findings contrast with the less positive findings of the randomized SAVE study (3). In contrast, our results are consistent with recently published data from a Danish historical cohort (22,135 patients with OSA), which showed that CPAP treatment was associated with lower mortality rates in middle-aged and elderly men after adjustment for multiple comorbidities, but not in women (5). Although in our population sex differences in the results seem to be related to a high heart failure prevalence among women using CPAP, further research is needed on the potentially different characteristics of OSA, and associated comorbidities, among women and men. Finally, several potential limitations should be noted. First, the data used in this study lack information about CPAP adherence. Second, it was not possible to control for undiagnosed OSA in control subjects, and, finally, the observational design means that potential confounding from uncontrolled factors such as socioeconomic status, level of health literacy and self-care, or level of delivered health care cannot be avoided. In conclusion, these findings suggest that CPAP treatment is associated with reductions in mortality at the population level, although only in men. Therefore, further analyses should be planned within the frame of precision medicine (6) to clarify which patients with OSA could benefit the most from CPAP treatment and whether CPAP might be detrimental in some specific patient subgroups. n Author disclosures are available with the text of this letter at www.atsjournals.org.